Current opinion in structural biology最新文献

英文中文

Orchestrating function: Concerted dynamics, allostery, and catalysis in protein tyrosine phosphatases 协调功能：蛋白酪氨酸磷酸酶的协调动力学、变构和催化作用。

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-04 DOI: 10.1016/j.sbi.2025.103125

Virgil A. Woods , Shivani Sharma , Alexis M. Lemberikman , Daniel A. Keedy

Protein tyrosine phosphatases (PTPs) are a family of enzymes that play critical roles in intracellular signaling and regulation. PTPs are conformationally dynamic, exhibiting motions of catalytic loops and additional regions of the structurally conserved catalytic domain. However, many questions remain about how dynamics contribute to catalysis and allostery in PTPs, how these behaviors vary among evolutionarily divergent PTP family members, and how mutations and ligands reshape dynamics to modulate PTP function. Recently, our understanding in these areas has expanded significantly, thanks to novel applications of existing methods and emergence of new approaches in structural biology and biophysics. Here we review exciting advances in this realm from the last few years. We organize our commentary both by experimental and computational methodologies, including solution techniques, avant-garde crystallography, molecular dynamics simulations, and bioinformatics, and also by scientific focus, including regulatory mechanisms, mutations and protein engineering, and small-molecule ligands such as allosteric modulators.

蛋白酪氨酸磷酸酶（PTPs）是一个在细胞内信号传导和调控中起关键作用的酶家族。PTPs是构象动态的，表现出催化环的运动和结构保守的催化域的附加区域。然而，关于动力学如何促进PTP的催化和变构，这些行为在进化不同的PTP家族成员中如何变化，以及突变和配体如何重塑动力学以调节PTP功能，仍然存在许多问题。最近，由于结构生物学和生物物理学中现有方法的新应用和新方法的出现，我们对这些领域的理解有了显著的扩展。在这里，我们回顾了过去几年在这一领域取得的令人兴奋的进展。我们通过实验和计算方法组织我们的评论，包括溶液技术，前卫晶体学，分子动力学模拟和生物信息学，以及科学焦点，包括调节机制，突变和蛋白质工程，以及小分子配体，如变构调节剂。

{"title":"Orchestrating function: Concerted dynamics, allostery, and catalysis in protein tyrosine phosphatases","authors":"Virgil A. Woods , Shivani Sharma , Alexis M. Lemberikman , Daniel A. Keedy","doi":"10.1016/j.sbi.2025.103125","DOIUrl":"10.1016/j.sbi.2025.103125","url":null,"abstract":"<div><div>Protein tyrosine phosphatases (PTPs) are a family of enzymes that play critical roles in intracellular signaling and regulation. PTPs are conformationally dynamic, exhibiting motions of catalytic loops and additional regions of the structurally conserved catalytic domain. However, many questions remain about how dynamics contribute to catalysis and allostery in PTPs, how these behaviors vary among evolutionarily divergent PTP family members, and how mutations and ligands reshape dynamics to modulate PTP function. Recently, our understanding in these areas has expanded significantly, thanks to novel applications of existing methods and emergence of new approaches in structural biology and biophysics. Here we review exciting advances in this realm from the last few years. We organize our commentary both by experimental and computational methodologies, including solution techniques, avant-garde crystallography, molecular dynamics simulations, and bioinformatics, and also by scientific focus, including regulatory mechanisms, mutations and protein engineering, and small-molecule ligands such as allosteric modulators.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"94 ","pages":"Article 103125"},"PeriodicalIF":6.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging paradigms in the lateral and transverse organization in biological membrane and their functional implications: Connecting the dots with biomolecular simulations 生物膜横向和横向组织的新范式及其功能含义：用生物分子模拟连接点

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-31 DOI: 10.1016/j.sbi.2025.103128

Anand Srivastava

Since the publication of the first papers in the early 1990s, molecular simulation as a reliable biophysical tool in the area of membrane biophysics has come a long way. Advances in simulation algorithms, coupled with exascale computing have pushed the size and time scales of biomolecular membrane simulations to scales where connections to experiments are made with higher fidelity. When integrated with experimental data in a theoretically well-grounded manner, current biomolecular simulations are providing indispensable insights that cannot be obtained through experiments alone. Here, I summarize some recent developments where simulations have allowed a deeper understanding in membrane spatiotemporal organization. I also discuss the need for transformative method developments to meet recent breakthroughs in experimental measurements at molecular scales.

自20世纪90年代初第一批论文发表以来，分子模拟作为一种可靠的生物物理工具在膜生物物理学领域取得了长足的发展。模拟算法的进步，加上百亿亿次计算，已经将生物分子膜模拟的大小和时间尺度推向了更高保真度的实验连接尺度。当以理论上有充分根据的方式与实验数据相结合时，当前的生物分子模拟提供了仅通过实验无法获得的不可或缺的见解。在这里，我总结了一些最近的发展，其中模拟允许对膜时空组织有更深的理解。我还讨论了变革方法发展的必要性，以满足最近在分子尺度上实验测量的突破。

引用次数: 0

Editorial overview of 3D genome chromatin organization and regulation 编辑概述三维基因组染色质组织和调控

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-30 DOI: 10.1016/j.sbi.2025.103123

Yuan He, Yawen Bai

引用次数: 0

Approaches for regulating enzyme activities: Recent advances in experiment and computation 调节酶活性的方法：实验和计算的最新进展

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-29 DOI: 10.1016/j.sbi.2025.103124

Qiang Cui

Major progress has been made in recent years in terms of strategies for regulating enzyme activities. Novel high-throughput enzyme kinetic assays and efficient computational methodologies enabled a deeper understanding of molecular mechanisms that dictate the activity of enzymes, which provide guidance to rational modulation of enzyme catalysis. Continued development of efficient screening, directed evolution technologies, and machine learning–driven protein engineering tools make it possible to tune enzyme activities without having to understand the detailed mechanism of catalysis regulation. By combining these two limiting approaches, the efficiency of enzyme regulation can be substantially improved as a mechanistic understanding can help reduce the size of design space before the ‘brute-force’ engineering approach takes over. We briefly discuss relevant advances in both experiment and computation and comment on future developments that can further enhance mechanistic understanding and engineering capability for broad applications.

近年来，在调节酶活性的策略方面取得了重大进展。新的高通量酶动力学分析和高效的计算方法使人们能够更深入地了解决定酶活性的分子机制，这为酶催化的合理调节提供了指导。高效筛选、定向进化技术和机器学习驱动的蛋白质工程工具的持续发展，使得无需了解催化调节的详细机制就可以调整酶的活性。通过结合这两种限制方法，酶调节的效率可以大大提高，因为在“暴力”工程方法接管之前，对机制的理解可以帮助减少设计空间的大小。我们简要地讨论了实验和计算的相关进展，并对未来的发展进行了评论，以进一步提高对机械的理解和工程能力，以实现广泛的应用。

引用次数: 0

A to-do list for realizing the sequence-to-function paradigm of proteins 实现蛋白质从序列到功能范式的待办事项清单

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-17 DOI: 10.1016/j.sbi.2025.103119

Chun Kit Chan , Christine Rajarigam , Patrick Jiang , Jacob Miratsky , Mustafa Demir , Melih Sener , Abhishek Singharoy

It has been a longstanding dream of the structural biology and molecular biophysics communities to determine protein functions directly from the amino acid sequences. Most methods available today, however, are homology- or library-based and often undermine determining divergent functions from comparable sequences or vice versa. The sequence-to-function relationship is intrinsically dependent on the biophysical space of protein dynamics, which can be potentially exploited to annotate function. But, despite three decades of active research, the space of molecular dynamics data remains grossly underpopulated. By employing surveys of the existing literature, we highlight this gray area in the context of machine learning methods. Thereafter, we share examples that point toward learning biophysical representations—or signatures—and combining them with integrative models as means to robustly associate sequence with function. The aim is to avoid having to compute protein dynamics for an impossible thousand years to achieve data completeness and generalization.

从氨基酸序列直接确定蛋白质的功能是结构生物学和分子生物物理学学界长期以来的梦想。然而，目前可用的大多数方法都是基于同源性或库的，并且经常破坏从可比序列中确定发散函数，反之亦然。序列-功能关系本质上依赖于蛋白质动力学的生物物理空间，这可以潜在地利用来注释功能。但是，尽管进行了三十年的积极研究，分子动力学数据的空间仍然严重不足。通过对现有文献的调查，我们强调了机器学习方法背景下的这一灰色地带。此后，我们将分享一些指向学习生物物理表征（或特征）的例子，并将它们与整合模型相结合，作为将序列与功能稳健关联的手段。其目的是避免为了实现数据的完整性和泛化而计算蛋白质动力学长达一千年。

{"title":"A to-do list for realizing the sequence-to-function paradigm of proteins","authors":"Chun Kit Chan , Christine Rajarigam , Patrick Jiang , Jacob Miratsky , Mustafa Demir , Melih Sener , Abhishek Singharoy","doi":"10.1016/j.sbi.2025.103119","DOIUrl":"10.1016/j.sbi.2025.103119","url":null,"abstract":"<div><div>It has been a longstanding dream of the structural biology and molecular biophysics communities to determine protein functions directly from the amino acid sequences. Most methods available today, however, are homology- or library-based and often undermine determining divergent functions from comparable sequences or vice versa. The sequence-to-function relationship is intrinsically dependent on the biophysical space of protein dynamics, which can be potentially exploited to annotate function. But, despite three decades of active research, the space of molecular dynamics data remains grossly underpopulated. By employing surveys of the existing literature, we highlight this gray area in the context of machine learning methods. Thereafter, we share examples that point toward learning biophysical representations—or signatures—and combining them with integrative models as means to robustly associate sequence with function. The aim is to avoid having to compute protein dynamics for an impossible thousand years to achieve data completeness and generalization.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103119"},"PeriodicalIF":6.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial overview: Toward cellular-scale modeling: Bigger and disordered 编辑概述：向细胞尺度建模：更大和混乱

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-17 DOI: 10.1016/j.sbi.2025.103121

Yuji Sugita, Robert J. Woods

引用次数: 0

Multicolor single-molecule FRET studies on dynamic protein systems 动态蛋白质系统的多色单分子FRET研究

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-14 DOI: 10.1016/j.sbi.2025.103117

Ecenaz Bilgen, Don C. Lamb

Förster resonance energy transfer (FRET) is a powerful tool for studying protein conformations, interactions, and dynamics at the single-molecule level. Multicolor FRET extends conventional two-color FRET by incorporating three or more fluorophores and thereby enabling a more comprehensive view of complex biomolecular processes. This technique allows for the simultaneous tracking of multiple structural changes, detecting intermediate states, and resolving heterogeneous population distributions. In this review, we discuss the recent advancements in fluorophore labeling strategies and data analysis methods that have significantly improved the precision and applicability of multicolor FRET in protein studies. We then end this review by showcasing recent applications for investigating protein folding and processes involved in gene regulation.

Förster共振能量转移（FRET）是在单分子水平上研究蛋白质构象，相互作用和动力学的强大工具。多色FRET扩展传统的双色FRET纳入三个或更多的荧光团，从而使复杂的生物分子过程的更全面的看法。该技术允许同时跟踪多个结构变化，检测中间状态，并解决异质种群分布。在这篇综述中，我们讨论了荧光团标记策略和数据分析方法的最新进展，这些方法显著提高了多色FRET在蛋白质研究中的精度和适用性。然后，我们通过展示研究蛋白质折叠和基因调控过程的最新应用来结束这一综述。

引用次数: 0

Probing molecular and biophysical mechanisms of RNA and protein phase transitions with simulations and theory 用模拟和理论探索RNA和蛋白质相变的分子和生物物理机制

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-14 DOI: 10.1016/j.sbi.2025.103120

Pin Yu Chew , Rosana Collepardo-Guevara

Biomolecular condensates play crucial roles in cellular organisation, regulating diverse biological functions as well as contributing to disease pathologies when phase separation is dysregulated. Computer simulations and theoretical approaches have emerged as powerful tools to probe the molecular mechanisms governing phase transitions in these systems. This review highlights recent advancements in computational methods, focusing on coarse-grained and all-atom molecular dynamics simulations, to elucidate the driving forces underlying protein and RNA condensate formation and how their stability and material properties can be regulated and tuned. Additionally, we address new strategies for designing synthetic condensates with tunable properties and leveraging predictive models to guide experimental studies. The integration of molecular simulations, with data-driven approaches and theory, has expanded our understanding of biomolecular condensates, offering novel insights into both fundamental biology and physics, as well as potential practical applications.

当相分离失调时，生物分子凝聚物在细胞组织中起着至关重要的作用，调节多种生物功能以及促进疾病病理。计算机模拟和理论方法已经成为探测这些系统中控制相变的分子机制的有力工具。这篇综述强调了计算方法的最新进展，重点是粗粒度和全原子分子动力学模拟，以阐明蛋白质和RNA凝聚物形成的驱动力，以及它们的稳定性和材料性质如何被调节和调整。此外，我们提出了设计具有可调性质的合成凝析油的新策略，并利用预测模型来指导实验研究。分子模拟与数据驱动的方法和理论的结合，扩大了我们对生物分子凝聚物的理解，为基础生物学和物理学以及潜在的实际应用提供了新的见解。

引用次数: 0

Are N-linked glycans intrinsically disordered? n链聚糖本质上是无序的吗？

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-10 DOI: 10.1016/j.sbi.2025.103118

Eliza Gazaway , Rajan Kandel , Oliver C. Grant, Robert J. Woods

The covalent attachment of oligosaccharides to asparagine side chains on protein surfaces (N-linked glycosylation) is a ubiquitous modification that is critical to protein stability and function. Experimental 3D structures of glycoproteins in which the N-linked glycans are well resolved are rare due to both the presumed flexibility of the N-linked glycan and to glycan microheterogeneity. To surmount these limitations, computational modeling is often applied to glycoproteins, particularly to generate an ensemble of 3D shapes for the N-linked glycans. While the number of glycoprotein modelling tools continues to expand, the available experimental data against which the predictions can be validated remains extremely limited. Here, we present our current understanding of the dynamic properties of N-linked glycans, with a particular focus on features that impact their presentation (orientation) relative to the protein surface. Additionally, we review the limits of experimental and theoretical studies of glycoproteins, and ask the question, “Are N-linked glycans intrinsically disordered?”.

低聚糖与蛋白质表面天冬酰胺侧链的共价连接（n -链糖基化）是一种普遍存在的修饰，对蛋白质的稳定性和功能至关重要。在糖蛋白的实验三维结构中，由于假定的n -连接的聚糖的灵活性和聚糖的微异质性，n -连接的聚糖被很好地分解是罕见的。为了克服这些限制，计算建模经常应用于糖蛋白，特别是为n链聚糖生成三维形状的集合。虽然糖蛋白建模工具的数量在不断增加，但用于验证预测的可用实验数据仍然非常有限。在这里，我们介绍了我们目前对n链聚糖的动态特性的理解，特别关注影响它们相对于蛋白质表面的呈现（取向）的特征。此外，我们回顾了糖蛋白的实验和理论研究的局限性，并提出了一个问题，“n -链聚糖本质上是无序的吗？”

{"title":"Are N-linked glycans intrinsically disordered?","authors":"Eliza Gazaway , Rajan Kandel , Oliver C. Grant, Robert J. Woods","doi":"10.1016/j.sbi.2025.103118","DOIUrl":"10.1016/j.sbi.2025.103118","url":null,"abstract":"<div><div>The covalent attachment of oligosaccharides to asparagine side chains on protein surfaces (<em>N-</em>linked glycosylation) is a ubiquitous modification that is critical to protein stability and function. Experimental 3D structures of glycoproteins in which the <em>N-</em>linked glycans are well resolved are rare due to both the presumed flexibility of the <em>N-</em>linked glycan and to glycan microheterogeneity. To surmount these limitations, computational modeling is often applied to glycoproteins, particularly to generate an ensemble of 3D shapes for the <em>N-</em>linked glycans. While the number of glycoprotein modelling tools continues to expand, the available experimental data against which the predictions can be validated remains extremely limited. Here, we present our current understanding of the dynamic properties of <em>N-</em>linked glycans, with a particular focus on features that impact their presentation (orientation) relative to the protein surface. Additionally, we review the limits of experimental and theoretical studies of glycoproteins, and ask the question, “Are <em>N-</em>linked glycans intrinsically disordered?”.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103118"},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Segmenting cryo-electron tomography data: Extracting models from cellular landscapes 分割低温电子断层扫描数据：从细胞景观中提取模型

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-07-10 DOI: 10.1016/j.sbi.2025.103114

Danielle A. Grotjahn

Cryo-electron tomography provides an unprecedented view of cellular architecture, yet extracting meaningful biological insights remains challenging. Segmentation is a crucial step in this process through its ability to identify structural relationships between subcellular components visible in cryo-electron tomography data. While segmentation pipelines were historically low throughput, recent advancements in deep learning have significantly improved their automation, accuracy, and scalability. This review explores how these innovations redefine best practices for segmentation and accelerate biological discovery. This article highlights the critical role of segmentation in unlocking the full potential of cryo-electron tomography—not only for resolving macromolecular structures but also for quantifying their impact on subcellular organization and function.

低温电子断层扫描提供了前所未有的细胞结构视图，但提取有意义的生物学见解仍然具有挑战性。分割是这一过程中的关键一步，因为它能够识别亚细胞成分之间的结构关系，在低温电子断层扫描数据中可见。虽然分割管道的吞吐量历来较低，但深度学习的最新进展显著提高了其自动化、准确性和可扩展性。这篇综述探讨了这些创新如何重新定义分割的最佳实践并加速生物发现。本文强调了分割在释放低温电子层析成像的全部潜力方面的关键作用——不仅用于解析大分子结构，而且用于量化它们对亚细胞组织和功能的影响。

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Current opinion in structural biology

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀